Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Butterworth:2011:10.1371/journal.pgen.1002260,
author = {Butterworth, AS and Braund, PS and Farrall, M and Hardwick, RJ and Saleheen, D and Peden, JF and Soranzo, N and Chambers, JC and Sivapalaratnam, S and Kleber, ME and Keating, B and Qasim, A and Klopp, N and Erdmann, J and Assimes, TL and Ball, SG and Balmforth, AJ and Barnes, TA and Basart, H and Baumert, J and Bezzina, CR and Boerwinkle, E and Boehm, BO and Brocheton, J and Bugert, P and Cambien, F and Clarke, R and Codd, V and Collins, R and Couper, D and Cupples, LA and de, Jong JS and Diemert, P and Ejebe, K and Elbers, CC and Elliott, P and Fornage, M and Franzosi, M-G and Frossard, P and Garner, S and Goel, A and Goodall, AH and Hengstenberg, C and Hunt, SE and Kastelein, JJP and Klungel, OH and Klueter, H and Koch, K and Koenig, IR and Kooner, AS and Laaksonen, R and Lathrop, M and Li, M and Liu, K and McPherson, R and Musameh, MD and Musani, S and Nelson, CP and O'Donnell, CJ and Ongen, H and Papanicolaou, G and Peters, A and Peters, BJM and Potter, S and Psaty, BM and Qu, L an},
doi = {10.1371/journal.pgen.1002260},
journal = {PLoS Genetics},
title = {Large-scale gene-centric analysis identifies novel variants for coronary Artery disease},
url = {http://dx.doi.org/10.1371/journal.pgen.1002260},
volume = {7},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity=0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse bioc
AU - Butterworth,AS
AU - Braund,PS
AU - Farrall,M
AU - Hardwick,RJ
AU - Saleheen,D
AU - Peden,JF
AU - Soranzo,N
AU - Chambers,JC
AU - Sivapalaratnam,S
AU - Kleber,ME
AU - Keating,B
AU - Qasim,A
AU - Klopp,N
AU - Erdmann,J
AU - Assimes,TL
AU - Ball,SG
AU - Balmforth,AJ
AU - Barnes,TA
AU - Basart,H
AU - Baumert,J
AU - Bezzina,CR
AU - Boerwinkle,E
AU - Boehm,BO
AU - Brocheton,J
AU - Bugert,P
AU - Cambien,F
AU - Clarke,R
AU - Codd,V
AU - Collins,R
AU - Couper,D
AU - Cupples,LA
AU - de,Jong JS
AU - Diemert,P
AU - Ejebe,K
AU - Elbers,CC
AU - Elliott,P
AU - Fornage,M
AU - Franzosi,M-G
AU - Frossard,P
AU - Garner,S
AU - Goel,A
AU - Goodall,AH
AU - Hengstenberg,C
AU - Hunt,SE
AU - Kastelein,JJP
AU - Klungel,OH
AU - Klueter,H
AU - Koch,K
AU - Koenig,IR
AU - Kooner,AS
AU - Laaksonen,R
AU - Lathrop,M
AU - Li,M
AU - Liu,K
AU - McPherson,R
AU - Musameh,MD
AU - Musani,S
AU - Nelson,CP
AU - O'Donnell,CJ
AU - Ongen,H
AU - Papanicolaou,G
AU - Peters,A
AU - Peters,BJM
AU - Potter,S
AU - Psaty,BM
AU - Qu,L
AU - Rader,DJ
AU - Rasheed,A
AU - Rice,C
AU - Scott,J
AU - Seedorf,U
AU - Sehmi,JS
AU - Sotoodehnia,N
AU - Stark,K
AU - Stephens,J
AU - van,der Schoot CE
AU - van,der Schouw YT
AU - Thorsteinsdottir,U
AU - Tomaszewski,M
AU - van,der Harst P
AU - Vasan,RS
AU - Wilde,AAM
AU - Willenborg,C
AU - Winkelmann,BR
AU - Zaidi,M
AU - Zhang,W
AU - Ziegler,A
AU - de,Bakker PIW
AU - Koenig,W
AU - Maerz,W
AU - Trip,MD
AU - Reilly,MP
AU - Kathiresan,S
AU - Schunkert,H
AU - Hamsten,A
AU - Hall,AS
AU - Kooner,JS
AU - Thompson,SG
AU - Thompson,JR
AU - Deloukas,P
AU - Ouwehand,WH
AU - Watkins,H
AU - Danesh,J
AU - Samani,NJ
DO - 10.1371/journal.pgen.1002260
PY - 2011///
SN - 1553-7390
TI - Large-scale gene-centric analysis identifies novel variants for coronary Artery disease
T2 - PLoS Genetics
UR - http://dx.doi.org/10.1371/journal.pgen.1002260
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000295419100015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/53986
VL - 7
ER -